The long-term objective of the project is to carry out molecular genetic investigations of photoreceptor processes using electroretinogram (ERG)-defective mutants of Drosophila. There are two main, related topics of investigation proposed in this application. One is to elucidate the mechanisms of excitation and regulation of the light-activated channel of Drosophila, TRP, by identifying proteins that potentially interact with TRP channels and attempting to clarify their functions. The other is to isolate and characterize two novel genes that, when defective, cause striking photoreceptor degeneration. The study of the excitation mechanism of the TRP channel is important, not only because it is the most important unsolved problem in Drosophila photoreceptor excitation, but also because the TRP protein has over 20 related proteins in mammals. At least two of these are expressed in the eye. Biological functions now beginning to be uncovered for some of these are both diverse and important. They range from temperature detection to tumor suppression, and some even show promise as early detectors of prostate cancer. Elucidation of how the Drosophila TRP channels work would provide insights into how these related mammalian channels work. Understanding how these mammalian channels function, in turn, could have important consequences in the therapy and management of health-related problems. Studying novel retinal degeneration genes of Drosophila are important because inherited retinal degeneration remains one of the most important causes of blindness in humans and the mechanisms of retinal degeneration often are conserved among different species. Drosophila is used in these studies because molecular and genetic studies can be much more effectively and precisely carried out in this organism than in any other animal organisms. Moreover, it has now been shown over and over again what is learned in Drosophila provide important insights into the corresponding processes in mammals.